Cancer Genetics: The goal of the program is to take cancer genetics research beyond the standard genotype-phenotype correlation toward understanding cross talk between genes and non-genetic influences on genes (systems genetics). Genes do not act in isolation and these types of interactions impact the resulting phenotype with profound implications in human cancer. Program faculty have outlined five strategic goals: (i) Genome-wide strategies, (ii) High penetrance cancer genes, (iii) Loss of genome integrity, (iv) Epigenetic processes, and (v) State-of-the-art infrastructure, both technology and bioinformatics. The Program is achieving their goals through program and program subset meetings, collaborative grants, cancer center investment in recruitment, technology development and pilot project funding. Highlights of research by Program investigators include creation of a novel mouse platform known as the Collaborative Cross, which randomizes the mouse genome to mimic human variation (Pardo Manuel de Villena, Threadgill, Pomp, Wang, Valdar). Perou and Sharpless have created the mouse phase I unit of genetically engineered pre-clinical mouse models for monitoring and developing phenotypic assays for cancer treatment. Evans and Berg have expanded the clinical genetics program and have embarked on a patient-centered project aimed at using next-generation genetic technology to look for disease-causing mutations in families where a Mendelian cancer susceptibility was suspected but not discovered. Threadgill and Pomp are part of the Mouse Models of Human Cancer Consortium with a project that focuses on colorectal cancer. Lieb continues to develop novel genomic approaches and Magnuson has challenged a long-standing epigenetic role for the non-coding RNA known as Xist. Proudly, Oliver Smithies was awarded the Nobel Prize for his pioneering work that underlies the program's use of cancer mouse models. Recruitment in statistical and human genetics, as well as computational approaches, has expanded the scope of the program, particularly its impact on the population and clinical sciences. Core facility development of high throughput sequencing has provided additional opportunities for participation in high priority NCI initiatives, e.g., phase II of the Cancer Genome Atlas (Perou, Chiang, Wright and Hayes). In 2009, the 39 program faculty investigators have 78 grants and $32.8 million (total $) in extramural support. Peer-reviewed research funding totals 62 grants and $29.7 million (total $), including 18 grants ($9.0 million) from the National Cancer Institute.